Process for manufacture of a thermochromic contact lens material

ABSTRACT

Disclosed in this specification is a process for manufacturing a thermochromic contact lens. The process includes (1) selecting a photoinitiator that absorbs at a first wavelength and at least one thermochromic dye that displays substantial absorption at the first wavelength when the dye is at a first temperature and exhibits at least an 80% reduction in absorbance at the first wavelength at a second temperature, (2) maintaining the reaction mixture at the second temperature and (3) providing cure light that includes the first wavelength.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/082,517 filed Apr. 8, 2011, now U.S. Pat. No. 8,877,103, which claimspriority to U.S. Provisional Patent Application No. 61/323,426, filedApr. 13, 2010.

FIELD OF THE INVENTION

This invention relates, in one embodiment, to a process formanufacturing contact lenses comprising at least one thermochromiccompound. More particularly, the process relates to a manufacturingprocess for photocuring polymerizable mixtures in the presence ofthermochromic compounds to produce contact lenses comprisingthermochromic compounds.

BACKGROUND

Precision spectral filters filter specific wavelengths of visible or UVradiation. This allows for the production of optical articles, such asglasses, which can be tailored to block specific wavelengths of light toproduce optical articles for different uses, including the protection ofthe cornea, lens and retina from specific harmful radiation wavelengths.For example, various sunglasses have been used to protect human eyesfrom strong light including photochromic glasses, polarized glasses andglasses for specific activities including shooting and fishing.Photochromic spectacles darken upon exposure to certain wavelengths oflight and typically exposure to ultraviolet (UV) light and brighten whenUV light is removed. Often, such photochromic spectacles include aprescription for vision correction.

Adapting certain technology, including photochromic technology tocontact lenses is more difficult than adapting the same technology tospectacles. Additional factors, such an oxygen permeability, comfort andfit of the resulting lens, must be taken into account. The manufacturingprocess of contact lenses is also more complicated. Typically, contactlenses are formed by irradiating a photoinitiator in the presence of oneor more polymerizable materials. In the case of photochromic contactlenses, it is desirable to include the photochromic dye in the reactivemixture containing the photoinitiator and polymerizable materials that,upon polymerization, forms the contact lens. Unfortunately, certaindyes, including photochromic dyes have the potential to interfere withthe activation of the photoinitiator.

Polymerizable mixtures may also be cured using other free radical basedchain reaction polymerization, including thermal polymerization.

SUMMARY OF THE INVENTION

The invention comprises, in one form thereof, a process formanufacturing contact lenses comprising at least one thermochromiccompound. The process includes (1) selecting a photoinitiator thatabsorbs radiation at a first wavelength and a thermochromic compoundthat absorbs radiation at the same first wavelength but does notsubstantially absorb at this wavelength at a second temperature, (2)maintaining the reaction mixture at the second temperature and (3)exposing the reaction mixture to radiation that includes the firstwavelength.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention is disclosed with reference to the accompanyingdrawings, wherein:

FIG. 1 is a flow diagram depicting one process of the invention;

FIGS. 2A and 2B are perspective and profile views of one pallet for usewith the invention;

FIG. 3 is are absorbance spectra of a photochromic dye, photoinitiator,and filters of one embodiment;

FIGS. 4A and 4B are absorbance spectra of a dye in an activated andunactivated state;

FIG. 5 depicts the profiles of various contact lenses cured at varioustemperatures;

FIG. 6 is a schematic representation of one apparatus for curing acontent lens;

FIGS. 7A to 7D are depictions of various contact lenses cured undervarious conditions described in Examples 5-8;

FIGS. 8A and 8B are graphs of the amount of residual monomer remainingin the contact lenses;

FIGS. 9A and 9B are absorbance spectra and rheology graphs of onecontact lens formation process;

FIGS. 10A and 10B are absorbance spectra and rheology graphs of anothercontact lens formation process; and

FIGS. 11A and 11B are absorbance spectra and rheology graphs of yetanother contact lens formation process.

Corresponding reference characters indicate corresponding partsthroughout the several views. The examples set out herein illustrateseveral embodiments of the invention but should not be construed aslimiting the scope of the invention in any manner.

DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT

Any chemical name preceded by (meth), for example (meth)acrylate,includes both the unsubstituted and methyl substituted compound.

Fixed light absorbing compounds are compounds which display temperatureindependent light absorption.

Referring to FIG. 1, one embodiment of the process, 100 is depicted thatbegins with step 102 wherein a photoinitiator and a photochromic dye areselected. Although it is theoretically possible to select aninitiator/photochromic dye pair that do not have any overlap in theirabsorption spectra, such pairs are difficult to find for use in contactlenses. In one embodiment, the present invention is directed toinitiator/thermochromic compound pairs that both absorb within anoverlapping wavelength range at least one temperature. In one embodimentthe initiator/dye pair displays overlapping absorbance at least onewavelength within the range of about 380 nm to about 780 nm.

Initiators generate free radicals that can initiate a chemical chainreaction. A photoinitiator is a compound that, upon exposure to certainwavelength of light, generates free radicals that can initiate achemical chain reaction. In one embodiment, the photoinitiator absorbswithin the visible range (about 380 nm to about 780 nm) of theelectromagnetic spectrum. Suitable visible light photoinitiators areknown in the art and include, but are not limited to aromaticalpha-hydroxy ketones, alkoxyoxybenzoins, acetophenones, acylphosphineoxides, bisacylphosphine oxides, and a tertiary amine plus a diketone,mixtures thereof and the like. Illustrative examples of photoinitiatorsare 1-hydroxycyclohexyl phenyl ketone,2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide(DMBAPO), bis(2,4,6-trimethylbenzoyl)-phenyl phosphineoxide (Irgacure819), 2,4,6-trimethylbenzyldiphenyl phosphine oxide and2,4,6-trimethylbenzoyl diphenylphosphine oxide, benzoin methyl ester anda combination of camphorquinone and ethyl 4-(N,N-dimethylamino)benzoate.Commercially available visible light initiator systems include Irgacure819, Irgacure 1700, Irgacure 1800, Irgacure 819, Irgacure 1850 (all fromCiba Specialty Chemicals) and Lucirin TPO initiator (available fromBASF). These and other photoinitators which may be used are disclosed inVolume III, Photoinitiators for Free Radical Cationic & AnionicPhotopolymerization, 2^(nd) Edition by J. V. Crivello & K. Dietliker;edited by G. Bradley; John Wiley and Sons; New York; 1998. The initiatoris used in the reaction mixture in effective amounts to initiatephotopolymerization of the reaction mixture, e.g., from about 0.1 toabout 2 parts by weight per 100 parts of reactive monomer.

In one embodiment visible light photoinitiators include alpha-hydroxyketones such as Irgacure® (e.g. Irgacure 1700 or 1800) available fromCIBA; various organic phosphine oxides, 2,2′-azo-bis-isobutyro-nitrile;diethoxyacetophenone; 1-hydroxycyclohexyl phenyl ketone;2,2-dimethoxy-2-phenylacetophenone; phenothiazine; diisopropylxanthogendisulfide; benzoin or benzoin derivatives; and the like. In oneembodiment, the initiator absorbs light and is activated at wavelengthsbelow about 420 nm.

In another embodiment, thermal initiation is used in place of or inconjunction with photoinitation. Examples of thermal initiators includelauroyl peroxide, benzoyl peroxide, isopropyl percarbonate,azobisisobutyronitrile, mixtures thereof and the like.

Thermochromic compounds are compounds that display temperature dependentlight absorption. Thermochromic compounds include compounds such asleuco dyes and liquid crystal particles which are generally used fortheir temperature dependent changes in light absorption as well ascompounds such as photochromic compounds which display changes in therate or degree to which they absorb light in their activated state.

Examples of thermochromic liquid crystals include cholesteryl nonanoateand cyanobiphenyls. Additional examples are disclosed in “LiquidCrystals”, D. Demus and H. Sackman, Gordon and Breach 1967. Examples ofleuco dyes include spirolactones, fluorans, spiropyrans, fulgides andcombinations thereof. The liquid crystals and leuco dyes may beincorporated into polymerizable mixtures as microcapsules.

Photochromic dye is any compound that is capable of transforming betweena first “clear,” “bleached” or “unactivated” ground state and a second“colored”, darkened or “activated” state in response to the absorptionof certain wavelengths of electromagnetic radiation (or “actinicradiation”). In one embodiment, the photochromic dye, when in anactivated state, absorbs within the visible range (380 nm to 780 nm) ofthe electromagnetic spectrum. Examples of suitable photochromic dyes areknown in the art and include, without limitation, the following classesof materials: chromenes, such as naphthopyrans, benzopyrans,indenonaphthopyrans and phenanthropyrans; spiropyrans, such as spiro(benzindoline) naphthopyrans, spiro (indoline) benzopyrans, spiro(indoline) naphthopyrans, spiro (indoline) quinopyrans and spiro(indoline) pyrans; oxazines, such as spiro (indoline) naphthoxazines,spiro (indoline) pyridobenzoxazines, spiro (benzindoline)pyridobenzoxazines, spiro (benzindoline) naphthoxazines and spiro(indoline) benzoxazines; mercury dithizonates, fulgides, fulgimides andmixtures of such photochromic compounds.

Additional suitable photochromic dyes include, without limitation,organo-metal dithiozonates, such as (arylazo)-thioformicarylhydrazidates, e.g., mercury dithizonates; and fulgides andfulgimides, naphthoxazines, spirobenzopyrans; polymerizablespirobenzopyrans and spirobenzopyrans; polymerizable fulgides;polymerizable naphthacenediones; polymerizable spirooxazines; andpolymerizable polyalkoxylated napthopyrans. The photochromic dyes may beused alone or in combination with one or more other appropriate andcomplementary photochromic dyes.

Still other useful photochromic dyes include indeno-fused naphthopyranschosen from an indeno[2′,3′:3,4]naphtho[1,2-b]pyran and anindeno[1′,2′:4,3]naphtho[2,1-b]pyran, which are more specificallydisclosed in US2009/0072206 and US2006/0226401 and those cited in U.S.Pat. No. 7,364,291, and combinations thereof. Other suitablephotochromic compounds are disclosed in U.S. Pat. No. 7,556,750, thedisclosure of which is incorporated by reference. Non-limiting examplesof suitable photochromic dyes include naphthopyrans such as those shownin Table 1. The dyes may include polymerizable functional groups suchthat they are copolymerized into the resulting contact lens. Examples ofpolymerizable functional groups include (meth)acrylates,(meth)acrylamides, vinyls and the like. In one embodiment, aphotochromic dye is selected that, when in an activated state, absorbsacross the visible spectrum but, when unactivated, absorbs below about430 nm and less than about 10% across the visible spectrum.

The amount of thermochromic compound used will be that effective toachieve desired reduction in percent transmission at the specificwavelengths where selected thermochromic compound is active. Theparticular amount used also will depend upon the coloring strength andmolar absorptivity of the selected compound(s), the lens materialselected as well as the thickness of the lens.

In another embodiment the contact lens may contain a mixture ofthermochromic compounds, at least one thermochromic compound in mixturewith other fixed light absorbing compounds, including pigments, dyes andUV absorbing compounds or may contain multiple layers of thermochromiccompounds, such as are used to make polarizing lenses.

Once the photoinitiator and thermochromic compound have been selected,step 104 is executed wherein a mixture of contact lens-forming materialsis disposed in a mold. Step 104 is explained in additional detail withreference to FIG. 2A and FIG. 2B.

Referring to FIG. 2A, reaction mixture 200 is disposed in mold 202 whichis supported by pallet 204. In one embodiment, the mold is athermoplastic optical mold, made from any suitable material including,without limitation, polypropylene, polystyrene, and/or Zeonor®: cyclicolefin polymer resins. In certain embodiments, the mold is selected tobe transparent to wavelengths that will activate the photoinitiator,thus permitting irradiation from the bottom side of the mold. In otherembodiments, such as those using thermal initiation, the mold 202 isoptically opaque. A “reaction mixture” is the mixture components,including, reactive components, diluent (if used), initiators,crosslinkers and additives which, when subjected to polymer formingconditions, form a polymer. Reactive components are the components inthe reaction mixture, which upon polymerization, become a permanent partof the polymer, either via chemical bonding or entrapment orentanglement within the polymer matrix. For example, reactive monomersbecome part of the polymer via polymerization, while non-reactivepolymeric internal wetting agents, such as PVP become part of thepolymer via entrapment. The diluent (if used) and any additionalprocessing aids do not become part of the structure of the polymer andare not part of the reactive components. Mixture 200 includes one ormore polymerizable monomers suitable for forming contact lenses. Suchmonomers are known in the art and are generally selected to producepolymerization products with high water and oxygen permeability.

The invention may be used to provide hard or soft contact lenses made ofany known lens material, or material suitable for manufacturing suchlenses. Preferably, the lenses of the invention are soft contact lenseshaving water contents of about 0 to about 90 percent, and in anotherembodiment between about 20 and about 75% water. In yet anotherembodiment the contact lenses of the present invention have a watercontent of at least about 25%. The lenses of the present invention mayalso have other desirable properties, including a tensile modulus ofless than about 200 psi, in some embodiments less than about 150 psi andin other embodiments less than about 100 psi. The lenses may furtherhave oxygen permeabilities of greater than about 50 psi, and in someembodiments greater than about 100 psi. It should be understood thatcombinations of the foregoing properties are desirable, and the abovereferenced ranges may be combined in any combination.

In one embodiment, the lenses are made of hydrophilic components,silicone-containing components and mixtures thereof to form polymerssuch as siloxanes, hydrogels, silicone hydrogels, and combinationsthereof. Material useful for forming the lenses of the invention may bemade by reacting blends of macromers, monomers, polymers andcombinations thereof along with additives such as polymerizationinitiators. Suitable materials include, without limitation, siliconehydrogels made from silicone macromers and hydrophilic monomers.

Reaction mixtures for making the contact lenses are well known and thecomponents of such mixtures are commercially available. Examplespolymers suitable for forming contact lenses include but are not limitedto etafilcon A, genfilcon A, lenefilcon A, polymacon, balafilcon,acquafilcon, comfilcon, galyfilcon, senofilcon, narafilcon andlotrafilcon. In another embodiment, contact lens formulations includeetafilcon, senofilcon, balafilcon, galyfilcon, lotrafilcon, comfilcon,filcon II 3, asmofilcon A, and silicone hydrogels, as prepared in U.S.Pat. No. 5,998,498; U.S. patent application Ser. No. 09/532,943, acontinuation-in-part of U.S. patent application Ser. No. 09/532,943,filed on Aug. 30, 2000, and U.S. Pat. No. 6,087,415, U.S. Pat. No.6,087,415, U.S. Pat. No. 5,760,100, U.S. Pat. No. 5,776,999, U.S. Pat.No. 5,789,461, U.S. Pat. No. 5,849,811, U.S. Pat. No. 5,965,631, U.S.Pat. No. 7,553,880, WO2008/061992, US2010/048847. These patents arehereby incorporated by reference for the hydrogel compositions containedtherein.

In one embodiment, the reaction mixture used is a HEMA based hydrogel,such as etafilcon A. Etafilcon A, disclosed in U.S. Pat. Nos. 4,680,336and 4,495,313 incorporated herein in their entireties by reference,generally is a formulation of 100 parts by weight (“pbw”) HEMA, about1.5 to about 2.5 pbw MAA, approximately 0.3 to about 1.3 pbw ethyleneglycol dimethacrylate, about 0.05 to about 1.5 pbw1,1,1,-trimethylolpropane trimethacrylate, and about 0.017 to about0.024 pbw of a visibility tint. The phrase “polymerizable monomers”includes monomers with large molecular weights, sometimes referred to asmacromers. A reaction mixture of different polymerizable monomers mayalso be used, resulting in the production of a co-polymer.

In one embodiment, mixture 200 also includes one or more selectedvisible light photoinitiators that are activated by exposure to visiblelight to initiate a chain reaction that causes the aforementionedmonomers to polymerize.

Mixture 200 further includes the selected thermochromic compound and inone embodiment photochromic dye that becomes colored upon exposure tolight but will revert to its original color shortly after the light isdiscontinued. In is unactivated (clear) state, the dye absorbs belowabout 430 nm and becomes activated. Once activated, the absorbance rangechanges to overlap with the visible spectrum (380-780 nm) and thusbecomes colored. This color, in turn, blocks the very wavelengths thatwould otherwise activate an photoinitiator that typically absorbs belowabout 420 nm

The presence of both the thermochromic compound and the photoinitiatorin the same reaction mixture can make controlled activation of thephotoinitiator problematic. Without wishing to be bound to anyparticular theory, applicants believe the activation of thethermochromic compound in the same spectral region as the photoinitiatorcauses the dye to at least partially “shield” the photoinitiator. Theincomplete activation of the initiator prevents curing and/or results ina non-uniform or anisotropic cure that causes material defects andstresses to form within the lens. These defects negatively impact themechanical and optical properties of the resulting contact lens. Oneembodiment of the present invention where the thermochromic compoundcomprises at least one photochromic compound, the process utilizesfilters to remove at least a portion of the wavelengths that result inexcitation of the dye while transmitting wavelengths that activate thephotoinitiator. See step 106 of FIG. 1. Step 106 is illustrated in moredetail in FIG. 3.

Suitable filters are selected based on the spectra of the photochromicdye and photoinitiator. Referring to FIG. 3, the spectrum of a dye 300is compared to the spectrum of a photoinitiator 302 and the spectrum ofthe light from a particular light source 304. A filter is used thatpermits transmission of select wavelengths of light (line 306). In theexample of FIG. 3, the photoinitiator is Irgacure® 1700, the lightsource is a TL 03 lamp and the photochromic dye is Dye-1. In thisinstance, one can preferentially activate the photoinitiator 302 in thepresence of dye 300 by providing cure light to the mixture at awavelength above 400 nm.

Although dye 300 is somewhat active between 400 nm and 420 nm,photoinitiator 302 is more responsive (i.e. has a larger molarabsorptivity) than the dye at such wavelengths. At least a portion ofthe wavelengths that activate the dye (e.g. those below 400 nm) havebeen omitted. In one embodiment, a long pass filter is used to omitwavelengths below about 400 nm but transmit wavelengths above about 400nm. In another embodiment, a different band pass filter is used totransmit only wavelengths within the range of about 400 nm to about 420nm, but remove wavelengths outside of this range. In yet anotherembodiment, a band pass filter selects wavelengths within the range ofabout 420 to about 440 nm. These wavelengths were selected based on thespectra presented in FIG. 3 for the particular photochromic dye andphotoinitiator illustrated therein. In other embodiments, differentfrequencies are selected to permit preferential excitation ofphotoinitiators with different absorption spectra. Examples of suitablefilters include SCHOTT GG420 filters or Encapsulite C20 filters. Inother embodiments, the light source is selected so as to provide curelight that does not irradiate within the absorption of the wavelength ofthe un-activated dye and filtering is unnecessary. Examples of suchlight sources include customized light emitting diodes (LEDs).

Applicants have discovered that the optical and mechanical properties ofthe resulting lens can be further improved by performing the curingprocess at a temperature where the thermochromic dye is inactive or lessactive (step 108 of FIG. 1). By way of example and without wishing to bebound by any particular theory, in the embodiment where thethermochromic compound is a photochromic compound, it is believed thatthe elevated temperature maintains the photochromic dye in a closed (notactivated) state. Thus, the absorbance spectrum of the photochromic dyeis different at room temperature when compared to the same spectrum atan elevated temperature. For photochromic dyes, this generally resultsin a decrease of the molar absorptivity at the very wavelengths thatoverlap with the λ_(max) of the photoinitiator. By maintaining anelevated temperature during the photocure, an increased amount of thedye is maintained in a closed state, thus effectively reducing theactivation of dye that interferes with the polymerization process. SeeFIG. 4A depicting naphthopyran Dye-1 in an inactive state and, in FIG.4B, the same dye in an activated state. In FIG. 4A, it is clear that theclosed dye is relatively inactive at wavelengths above 420 nm. Incontrast, FIG. 4B shows the activated dye absorbs at wavelengths above420 nm. A series of photochromic contact lenses were cured at varioustemperatures using filtered light. See examples 1 to 4 described below.FIG. 5 depicts profiles of these lenses.

In another embodiment where the thermochromic dye is a leuco dye, suchas spirolactones (such as crystal violet lactone), fluorans,spiropyrans, and fulgides, in combination with weak acids such asbisphenol A, parabens, 1,2,3-triazole derivates, and 4-hydroxycoumarin,cure may be conducted at temperatures between about 5 and about 60° C.In yet another embodiment, where the thermochromic dye is a liquidcrystal, such as such as cholesteryl nonanoate or cyanobiphenyl, thecure may be conducted at temperatures between about 10 and about 80° C.

Referring to the series of lens cross sections depicted in FIG. 5,lenses cured at 45° C. (first image, left) showed poor curing and hadinverted cross sections that were unacceptable for use on a human eye.Lenses cured at 50° C. showed some degree of improvement (second imagefrom the left). Lenses cured at 55° C. showed further improvement (thirdcross section). Lenses cured at 65° C. displayed only minor flatteningin cross section and were found to provide acceptable optics. Theseresults demonstrate an improvement in contact lens profile and opticswhen the lenses are cured at an elevated temperature. Accordingly, giventhe teaching of this application desired temperature ranges can beselected to produce acceptable profiles and optics for a range ofparticular reaction mixtures.

By way of illustration, when photochromic dye (such as Dye-1, anaphthopyran photochromic compound shown in Table 1) is used, curetemperature ranges of about 55° C. to about 90° C. may be used. Inanother embodiment, a temperature range of about 65° C. to about 80° C.is used. In yet another embodiment a temperature of about 80° C. isused. Other dyes may have different preferred temperature ranges.

Applicant has also discovered that, although filtering the light andelevating the temperature improves the properties of the resultinglenses, at least in some instances, these are not the only factors.Contact lens properties can be further improved by balancing the lightreceived by the mixture 200 on the exposed side 206 and mold-contactingsides 208. See FIG. 2B. The precise conditions necessary to balance theintensities will depend upon the composition and thickness of thereaction mixture, the composition of the pallet and the nature of thefilter(s) and light source(s). After benefiting from reading thisspecification one of ordinary skill can determine the optimum balancingconditions for a particular formulation.

In some embodiments, for example for contact lenses with lowthermochromic compound concentrations, special balancing of lightintensity may not be necessary. The mixture is sufficiently thin suchthat the light intensity at the exposed surface and the mold-contactingsides are substantially the same. In these instances, the cured contactlens that results is adequate. Similarly, in some embodiments, it ispossible to omit any special balancing by restricting the thermochromiccompound to a particular region of the lens (e.g. a pupil-onlythermochromic lens).

In certain instances, the intensity of the light at the mold-contactingside is substantially less than the intensity at the exposedsurface—presumably due to absorption of the light by the thermochromiccompound as the light passes through the mixture. In these situations,the profile of the resulting lens is less than desirable. A secondarylight source can be added to illuminate from underneath an opticallytransparent mold to properly balance the light intensities. FIG. 6depicts such a system.

Referring to FIG. 6, two or more filters 600, 602 are used to bothfilter the wavelength and balance the intensity of light emitted fromone or more light sources 604, 606 before such light illuminatesreaction mixture 200. The pallet 204 permits the wavelengths used toactivate the photoinitiator by passing through the bottom of the pallet,thereby allowing the reaction mixture within mold 202 to be illuminatedfrom both the exposed side 206 and the mold-contacting side 208 (seeFIG. 2B). The light sources, filters, and pallet are arranged such thatequal intensities of light are delivered to both the exposed andmold-contacting sides of the mixture. In one embodiment, not shown, thepallet 204 functions as a filter and removes certain wavelengths, thusobviating the need for filter 602.

In some embodiments, the intensity of one of the light sources isincreased to adjust for a loss of light intensity between the lightsource and the mixture 200. For example, in such an embodiment, bottomlight source 606 may have an intensity greater than top light source 604to adjust for the loss of light intensity due to the bottom lighttraveling through or shielded by the pallet 204. By way of illustrationand not limitation, the intensity of top light source 604 may be about 1mW/cm² while the intensity of bottom light source may be about 2 mW/cm².Differing intensity values are selected depending on the amount of lightblocked by the respective filters and the transmissivity or shielding ofthe pallet 204. Similarly, filters that reduce the intensity of thelight can be used to balance the intensity of the light that actuallyreaches the reaction mixture.

FIGS. 7A to 7E illustrate the effects of balanced or misbalancedillumination. FIG. 7A shows the desired profile of a properly formedcontact lens that does not include a photochromic dye. FIG. 7B shows theprofiles of contact lenses made using no filter and curing only from thetop side. FIG. 7C shows the profiles of contact lenses made using afilter and curing only from the top side. Although not visible in FIG.7C, the lens is inverted. FIG. 7D shows the profiles of contact lensesmade by curing from both sides using a filter, but with unbalanced lightintensities. FIG. 7E, which closely approximates the desired profile ofFIG. 7A, shows the profiles of contact lenses made by curing from bothsides using a filter with balanced light intensities. See examples 5 to9.

Once curing is completed, the lens is released from the mold and may betreated with a solvent to remove the diluent (if used) or any traces ofunreacted components. In one embodiment the solvent removal is conductedusing a primarily aqueous solution. The lens is then hydrated to formthe hydrogel lens.

Using the techniques described above, several forms of contact lensescan be made. In some embodiments, the thermochromic compound ishomogenously dispersed throughout the resulting contact lens. In such anembodiment, the entire contact lens is thermochromic. In otherembodiments, only the central portion of the resulting contact lensincludes the thermochromic compound. Since the central portion restsatop the pupil, the resulting contact lens is a pupil-only thermochromiccontact lens. The central portion, or central circular area may be thesame size as the optic zone, which in a typical contact lens is about 9mm or less in diameter. In one embodiment, the central circular has adiameter of between about 4 and about 9 mm and in another between about6 and about 9 mm in diameter and in another embodiment between about 6and about 8 mm.

The dye can be placed using a variety of techniques to provide a regionof a specified diameter. For example, the composition comprising the dyemay be applied to at least a portion of a molding surface via padprinting, ink jetting, spin coating and the like. In these embodimentsthe dye composition may comprise additional components known to beuseful including binding polymers which may be reactive or non-reactive,solvent, and optionally polymerizable components, chain transfer agents,initiators and combinations thereof. The dye composition may react withthe reactive mixture, or may swell and become entangled by the reactivemixture. If the dye composition is reactive, it may be partially orfully cured prior to dispensing the reactive mixture into the mold. Ifthe dye composition is non-reactive it may be desirable to evaporatesome or all of the solvent prior to dispensing the reactive mixture. Thetype and concentration of the non-dye components of the dye compositionswhich are known in the art may be used in the present invention.Examples include those disclosed in EP1448725, WO01/40846, U.S. Pat. No.5,658,376, US20090244479, WO2006/110306 and U.S. Pat. No. 6,337,040.

If an initiator is included in the dye composition the initiator andthermochromic compound are selected to have absorption profiles which donot substantially overlap at the selected cure temperature. Multiplelayers of dye composition may be applied to the mold, and the layers maycontain no thermochromic, the same thermochromic compound or differentthermochromic compounds. An example of this embodiment is applyingalternating layers of dye composition, each containing a liquid crystal,to form a polarized contact lens. In this embodiment, the alternatinglayers are cured under different conditions to provide layers in whichthe liquid crystals have alternating orientations, creating the desiredpolarizing effect. In another embodiment multiple layers of the samethermochromic compound are applied, each centered, but having adifferent diameter, thereby producing a lens with a graduatedconcentration of thermochromic compound.

After the cure composition is precured or the solvent evaporated, thereactive mixture is dosed to the mold as described above. The reactivemixture may comprise at least one additional thermochromic compound,which may be the same or different than the thermochromic compound usedin the dye composition layer. Alternatively, the reactive mixture may befree from thermochromic compounds. After the reactive mixture is dosed,the reactive mixture is cured.

Examples of suitable diameters include 4 mm, 6 mm, 9 mm and 11.4 mm. Inone embodiment the reactive mixture comprising the thermochromic dye isdeposited or dispensed via microdosing, such as disclosed in U.S. Pat.No. 7,560,056, and U.S. application Ser. No. 13/082,447, entitled“Pupil-Only Photochromic Contact Lenses Displaying Desirable Optics andComfort”, co-filed on Apr. 8, 2011.

To support the theory of operation, several experiments were conductedin which the time required to cure the mixture was measured as afunction of increased dye concentration. The results of theseexperiments demonstrated that higher dye concentration resulted inprolonged cure times. At a dye concentration of about 3% (MXP7-1631 dye)the mixture did not cure at a temperature of 40° C. See Example 9. Thissupports the hypothesis that the dye interferes with the activation ofthe photoinitiator.

To further support the theory of operation, the residual monomerconcentration of a series of lenses were made with and without padprinting of a photochromic dye. The lenses were cured without beinghydrated as the reaction mixture passed through a cure tunnel where theywere irradiated with light as they passed through various zones. Sampleswere removed from the apparatus and tested for residual photoinitiatorand residual monomer after passing through a certain number of zones.Thus, a sample that was removed after passing through five cure zonesexperienced a longer residence time than a sample that was removed afterpassing through two cure zones. See example 11.

The results, shown in FIG. 8A, show the photochromic dye is inhibitingthe initiator from starting a free radical polymerization. Those sampleswhere a photochromic dye was present show significantly largerconcentrations of unpolymerized monomer relative to the correspondingcontrol that lacked a photochromic dye. Likewise, FIG. 8B shows theconcentration of the photoinitiator is larger when the photochromic dyeis present. It is noteworthy that, when a photochromic dye is used, theconcentration of the photoinitiator achieved a stead-state concentrationthat never reaches zero or otherwise unifies with the control.

Similarly, rheology data was obtained for photochromic lenses made withand without filters. See Example 11. The results (FIGS. 9A and 9B) showthe gel point differences between lenses made with, and without, aphotochromic dye.

FIG. 9A illustrates spectra of an unactivated photochromic dye (line900), a photoinitiator (line 904) and a filtered light source thatremoved wavelengths below 380 nm (line 902, λ_(max) around 400 nm). FIG.9B depicts rheology data from a photochromic lens (line 906) and anon-photochromic control (line 908) cured using the conditions of FIG.9A. The interference from the photochromic dye causes the modulus (G) tobuild more slowly than a corresponding monomer cured without dyepresent, lines 906 and 908 respectively. The control (908) exhibited a95% conversion gel point of 37 seconds (point 908 a) and a 99%conversion gel point at point 908 b. This gap in % conversion at gelpoint shows significant differences between the photochromic lens andthe target control lens. The resulting photochromic polymers were deemedunsatisfactory for making contact lenses.

FIG. 10A is similar to FIG. 9A, but differs therefrom in that adifferent filter is used. In FIG. 10A, filtered light 1000 haswavelengths below 400 nm removed. FIG. 10B depicts rheology data from aphotochromic lens (line 1002) and a non-photochromic control (line 908)cured using the conditions of FIG. 10A. Compared to FIG. 9B, the twolines 1002, 908 are substantially closer and thus the resultingphotochromic lenses more closely match the control lens. The resultingphotochromic lenses were deemed satisfactory. The 95% conversion gelpoint (1002 a) and 99% conversion gel point (1002 b) are shown.

FIG. 11A illustrates spectra of an unactivated photochromic dye (line900), a photoinitiator (line 904) and a light source (line 1100, λ_(max)around 440 nm). Light source 1100 removes wavelengths below 420 nm. FIG.11B depicts a rheology data from photochromic lens (line 904) and anon-photochromic control (line 900) cured using the components of FIG.11A. Thus, the light source and filters removed wavelengths below about420 nm where the dye is most responsive. When the lower wavelengths wereremoved by the filter, the activation of the dye was minimized and themodulus of the photochromic lens 904 became more like that of thecontrol 900.

EXAMPLES

TABLE 1 Common abbreviations Abbreviation Compound Dye-1

Dye-2

Dye-3

Dye-4

TMPTMA trimethylolpropane trimethacrylate EDGMA ethyleneglycoldimethacrylate MAA methacrylic acid HEMA 2-hydroxyethylmethacrylateNorbloc 2-(2′-hydroxy-5-methacrylyloxyethylpheny1)-2H-benzotriazoleGlucam 20 ethoxylated methyl glucose etherFive formulations were utilized in the follow examples. The percentcomposition of each sample is shown in Table 2:

TABLE 2 A Component (control) B C D E Dye-1 0 2.1 2.8 1.2 2.8 Irgacure ®1.33 1.33 1.33 0 0 1700 (initiator) Irgacure ® 819 0 0 0 0.28 0.28(initiator) TMPTMA 0.09 0.09 0.09 0.09 0.09 EDGMA 0.77 0.77 0.77 0.770.77 MAA 1.94 1.94 1.94 1.94 1.94 HEMA 94.92 93.72 92.12 94.77 93.17Norbloc 0.95 0.95 0.95 0.95 0.95

The components listed in Table 2 were mixed with Glucam 20 in thefollowing amount 55 wt % monomer with 45 wt % diluent.

Example 1—Cure Temperature of 45° C.

A front curve mould (Zeonor) was pad printed with a dye base formed from7% Dye-1 and 93% clear base (49.4 wt % Isopropyllactate, 12.4 wt %1-Ethoxy-2-propanol, 0.9 wt % 1-Octanethiol, 1.63 wt % Glycerol, 35 wt %HEMA, 0.48% methacrylic acid, and 0.21 wt %Azobis-(2-methylbutyronitrile) (AMBM). The clear base was made by addingthe 1-octanethiol, monomers and solvents, except for about 50-100 cc ofthe isopropyllactate, were mixed in a 5 liter blue cap bottle andstirred for 10 minutes. The mixture was then poured into a 5 L stainlesssteel reactor with stirrer and nitrogen. The mixture was stirred andheated for approximately 25 min. until the temperature was 68° C. Afterthe temperature was stabilized at 68° C., the AMBN was dissolved in theremaining isopropyllactate and added while opening the nitrogen bleed.The polymerization was allowed to proceed for 16-24 hours after whichthe temperature was increased to 80° C. and the reaction was completed.The mixture was then allowed to equilibrate to room temperature.

The diameter of the print was 11.44 mm. The front and back of the curvemoulds were degassed with nitrogen. The front curve mould was dosed witha reactive monomer mix that contained Control A (see Table 2) no dye inRMM. A base curve mould was placed on the front curve containing monomerand the assembled moulds were moved to a cure box and thereafter heatedto a cure temperature of 45° C. The system was allowed to equilibratefor five minutes. Once equilibrated, the system was cured at 3.5 mW/cm²with Philips TL03 lamps using CG420 filter for ten minutes. The basecurve mould was removed and the front curve was hydrated in DI water at70° C. for ten minutes. The resulting lenses were subjected to customarypackaging and sterilization processes. The lenses were cross-sectionedand an image was obtained. The image is shown in FIG. 5.

Example 2—Cure Temperature of 50° C.

Example 2 was conducted in a substantially identical fashion as Example1 except in that the cure temperature was 50° C. The lenses werecross-sectioned and an image was obtained. The image is shown in FIG. 5.

Example 3—Cure Temperature of 55° C.

Example 3 was conducted in a substantially identical fashion as Example1 except in that the cure temperature was 55° C. The lenses werecross-sectioned and an image was obtained. The image is shown in FIG. 5.

Example 4—Cure Temperature of 65° C.

Example 2 was conducted in a substantially identical fashion as Example1 except in that the cure temperature was 65° C. The lenses werecross-sectioned and an image was obtained. The image is shown in FIG. 5.

Examples 5 8

The front and back curve moulds (Zeonor) were degassed with nitrogen.For Examples 6-8, the front curve mould was dosed with a reactivemonomer mix containing 2.1% Dye-1 (Formulation B, Table 2). For Example5 (control) Formulation A was dosed into the front curve. A base curvemould was placed on the front curve containing monomer mix. Theassembled moulds were moved to a cure box and heated to 65° C. Theassembly was allowed to equilibrate for five minutes. Once equilibrated,the system was cured with Philips TL03 lamps and CG420 filter for tenminutes at the cure intensity and cure set-ups specified in Table 3. Thebase curve mould was removed and the front curve was hydrated in DIwater at 70° C. for ten minutes. The resulting lenses were subjected tocustomary packaging and sterilization processes.

TABLE 3 Bottom Top intensity intensity Xsection Ex. # Filter (mW/cm²)(mW/cm²) Fig. # appearance 5 Yes 3 0 7A Normal 6 Yes 0 7B Rolled 7 Yes2.8 0.8 7C Inverted, flared 8 Yes 2.8 2.8 7D

The cross sections of the lenses made in Examples 5-8 are shown in FIGS.7A-D. FIG. 7A is the cross-section of the lens of Example 5, formed withno photochromic dye, and displays a smoothly curved cross sectionindicative of a well formed spherical contact lens. FIG. 7B is the crosssection of a lens formed with photochromic dye and cure from the toponly. The lens cross section is rolled into a tube. This indicatesuneven curing and shows the impact of the photochromic dye on curing inthis Example is not controlled by use of filters alone. FIGS. 7C(Example 7) and D (Example 8) show the cross sections for lenses madewith curing on both sides. In 7C the lens is inverted, but displays asmooth arc, a substantial improvement compared to Figure B. In FIG. 7D,the cross section for the lens cured with balanced intensity and filterson both sides, lenses with smooth, curved cross sections were obtained.

Example 9—High Dye Concentrations Prevents Curing

The photo-polymerization reaction of Formulations A-E were monitoredwith an ATS StressTech rheometer (available from ATS RheoSystems, 52Georgetown Road, Bordentown, N.J. 08505) equipped with a photo-curingaccessory, which included a temperature-controlled cell with a quartzlower plate and an aluminum upper plate, and an OmniCure mercury arclamp (available from EXFO Photonic Solutions Inc., 2260 Argentia Rd.,Mississauga, ON L5N 6H7 CANADA) with 420 nm band pass filter (availablefrom Andover Corporation, 4 Commercial Drive, Salem, N.H. 03079-2800USA) situated beneath the quartz plate. The intensity of the radiation,measured at the surface of the quartz window with an IL1400A radiometerand XRL140A sensor (available from International Light, Inc., 17 GrafRoad, Newburyport, Mass. 01950), was regulated at 4.5±0.5 mW/cm². Eachformulation was evaluated at 40° C., 55° C. and 70° C.

After approximately 0.25 mL of the reactive monomer mix was placed onthe lower plate of the rheometer, the 25 mm diameter upper plate waslowered to 0.500±0.001 mm above the lower plate, where it was held untilafter the reaction reached the gel point. The sample was allowed toreach thermal equilibrium (˜5 minutes, determined by the leveling-off ofthe steady shear viscosity of the sample as it warmed up) before theOmniCure was turned on and the reaction begun. During this time, whilethe sample was reaching thermal equilibrium, the sample chamber waspurged with nitrogen gas at a rate of 400 sccm. After this initial purgethe oxygen level in the sample chamber was monitored at 0.5±0.1% with aCheckPoint O₂ sensor (available from PBI Dansensor, available fromTopac, 101 Derby St., #203 Hingham, Mass. 02043). During the reactionthe rheometer continuously monitored the strain resulting from anapplied dynamic stress (fast oscillation mode), where time segments ofless than a complete cycle were used to measure the strain at theapplied sinusoidal stress (applied at a frequency of 1.0 Hz). Thedynamic shear modulus (G′), loss modulus (G″), and gap height weremonitored as a function of exposure time. As the reaction proceeded theshear modulus increased from <1 Pa to >0.1 MPa, and tan δ(=G″/G′)dropped from near infinity to less than 1. For many reactivecrosslinking systems the gel point is defined as the time at which tanδ=1 (the crossover point when G′=G″). At the time that G′ reached 100 Pa(shortly after the gel point), the restriction of the gap height on theupper plate was removed (Autotension Mode: Tension=0) so that the gapbetween the upper and lower plates could change as the reactive monomermix shrank during cure, and the stress due to shrinkage was kept at aminimum. A measurement of the change in gap provides an estimate of theamount of shrinkage caused by the polymerization reaction. After a10-minute exposure the OmniCure was turned off (i.e., the cure wasterminated).

The rheology results for each of the formulations evaluated are shown inTable 4, below.

TABLE 4 Rheology results A Temp Data (control) B C D E 40° C. Gel point30.5 32.7 n/a 99.0 n/a (seconds) Modulus 3.745 1.837 n/a 1.050 n/a(×10⁵) 55° C. Gel point 29.0 69.0 128.5 68.5 141.5 (seconds) Modulus2.529 1.678 0.430 1.676 0.277 (×10⁵) 70° C. Gel point 18.0 57.0 101.562.0 95.5 (seconds) Modulus 2.216 1.972 0.597 1.705 0.393 (×10⁵)

Samples C and E failed to cure at 40° C. These samples contained 2.8%photochromic dye.

Example 10—Monitoring Polymerization Progress by Tunnel Zone

A protocol was executed to determine the rate of consumption for lensesthat were pad-printed with a dye composition containing approximately 7%of Dye-1 and 93 wt % of the clear base described in Example 2 incomparison to lenses that were not pad-printed with the dye composition.Formulation A from Table 2 was dispensed in the pad-printed mold. Lenseswere cured with both high (8 mW/cm²) and low (4 mW/cm²) intensity curesfor comparison.

The experiment was carried through as follows: Closed pad printed, lensmolds containing the monomer mixes were loaded into the cure tunnel.Once the tunnel was full, the machine was completely stopped and palletsfor each row were removed out of the tunnel and labeled with theirlocation. The location of the pallet corresponds to the amount of lightthe lens was exposed to in the process. This process was repeated untilthe desired amount of samples was collected for each of the monomersmixtures and light intensities tested. The results are depicted in FIGS.8A and 8B.

Example 11

The photo-polymerization reaction for each of the Formulation C, listedin Table 2, was monitored with an ATS StressTech rheometer (ATSRheoSystems, 52 Georgetown Road, Bordentown, N.J. 08505) equipped with aphoto-curing accessory, which consisted of a temperature-controlled cellwith a quartz lower plate and an aluminum upper plate, and an OmniCuremercury arc lamp (EXFO Photonic Solutions Inc., 2260 Argentia Rd.,Mississauga, ON L5N 6H7 CANADA) with a band pass filter (AndoverCorporation, 4 Commercial Drive, Salem, N.H. 03079-2800 USA) situatedbeneath the quartz plate. The intensity of the radiation, measured atthe surface of the quartz window with an IL1400A radiometer and XRL140Asensor (International Light, Inc., 17 Graf Road, Newburyport, Mass.01950), was regulated at 4.5±0.5 mW/cm². The temperature was controlledat 60.0±0.1° C.

After approximately 0.25 mL of the reactive monomer mix was placed onthe lower plate of the rheometer, the 25 mm diameter upper plate waslowered to 0.500±0.001 mm above the lower plate, where it was held untilafter the reaction reached the gel point. The sample was allowed toreach thermal equilibrium (˜5 minutes, determined by the leveling-off ofthe steady shear viscosity of the sample as it warmed up) before theOmniCure was turned on and the reaction begun. During this time, whilethe sample was reaching thermal equilibrium, the sample chamber waspurged with nitrogen gas at a rate of 400 sccm. After this initial purgethe oxygen level in the sample chamber was monitored at 0.5±0.1% with aCheckPoint O₂ sensor (PBI Dansensor, available from Topac, 101 DerbySt., #203 Hingham, Mass. 02043). During the reaction the rheometercontinuously monitored the strain resulting from an applied dynamicstress (fast oscillation mode), where time segments of less than acomplete cycle were used to measure the strain at the applied sinusoidalstress (applied at a frequency of 1.0 Hz). The dynamic shear modulus(G′), loss modulus (G″), and gap height were monitored as a function ofexposure time. As the reaction proceeded the shear modulus increasedfrom <1 Pa to >0.1 MPa, and tan δ(=G″/G′) dropped from near infinity toless than 1. For many reactive crosslinking systems the gel point isdefined as the time at which tan δ=1 (the crossover point when G′=G″).At the time that G′ reached 100 Pa (shortly after the gel point), therestriction of the gap height on the upper plate was removed(Autotension Mode: Tension=0) so that the gap between the upper andlower plates could change as the reactive monomer mix shrank duringcure, and the stress due to shrinkage was kept at a minimum. Ameasurement of the change in gap provides an estimate of the amount ofshrinkage caused by the polymerization reaction. After a 10-minuteexposure the OmniCure was turned off (i.e., the cure was terminated).

The results are shown in FIGS. 9-11, which show the gel point and timeto 95% conversion differences between lenses made with the sameinitiator, but varying filters and photochromic dye concentrations. Ascan be seen by comparing FIGS. 9B, 10B and 11B, which show the modulusbuilds for the various polymers made in Example 11 (G′ v. time), whenfilters are used which block wavelengths where the photochromic dyedisplays absorbance, the efficiency of conversion is improved.

While the invention has been described with reference to preferredembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted forelements thereof to adapt to particular situations without departingfrom the scope of the invention. Therefore, it is intended that theinvention not be limited to the particular embodiments disclosed as thebest mode contemplated for carrying out this invention, but that theinvention will include all embodiments falling within the scope andspirit of the appended claims.

What is claimed is:
 1. A process for manufacturing a contact lenscomprising at least one photochromic compound consisting essentially ofthe steps of: selecting a photoinitiator which absorbs at a firstwavelength; selecting a photochromic dye which displays substantialabsorption at the first wavelength when the dye is at a firsttemperature and but is in an inactivated state at a second temperature;dispensing a reaction mixture into a mold, the mixture comprising atleast one polymerizable monomer, the photoinitiator and the photochromiccompound; warming the reaction mixture to said second temperature, tomaintain the photochromic compound in the inactivated state at the firstwavelength; curing the reaction mixture at said second temperature toform a photochromic contact lens by exposing the mixture to radiationthat include the first wavelength.
 2. The process as recited in claim 1,wherein the first temperature is about 25° C. and the second temperatureis at least about 40° C.
 3. The process as recited in claim 1, whereinthe photochromic compound is a polymerizable photochromic dye thatcopolymerizes with the at least one polymerizable monomer during thestep of curing the mixture.
 4. The process as recited in claim 1,wherein the photochromic compound is homogeneously dispersed throughoutthe contact lens.
 5. The process as recited in claim 1, wherein thephotochromic compound is disposed in a central circular area having adiameter of about 1 to about 9 mm centered at a geometric center of thecontact lens and the central circular area is surrounded by a regionthat is substantially free of the photochromic dye, thus forming apupil-only contact lens.
 6. The process as recited in claim 1, whereinthe first wavelength is between 380 nm to 780 nm.
 7. The process asrecited in claim 1, wherein the first wavelength is between 400 nm to500 nm.
 8. The process as recited in claim 1, wherein the firstwavelength is between 420 nm to 480 nm.
 9. The process as recited inclaim 1, wherein the temperature of the warming step is between 55° C.and 75° C.
 10. The process as recited in claim 1, wherein thetemperature of the warming step between 60° C. and 70° C.
 11. Theprocess of claim 1 wherein said mold is exposed to radiation from a topand bottom side of the mold.
 12. The process of claim 1 wherein saidradiation is balanced from the top and bottom sides of the mold.
 13. Theprocess of claim 1 wherein said curing step further comprises filteringout wavelengths outside the range of about 400 nm to about 420 nm. 14.The process of claim 1 wherein said curing step further comprisesfiltering out wavelengths outside the range of about 420 to about 440nm.
 15. The process of claim 1 wherein said radiation is provided bylight emitting diodes.
 16. The process of claim 1 wherein said radiationomits at least a portion of the wavelengths absorbed by the photochromiccompound in the inactivated state.
 17. The process of claim 1 whereinsaid radiation omits all the wavelengths absorbed by the photochromiccompound in the inactivated state.